Alternative ion channel splicing in mesial temporal lobe epilepsy and Alzheimer's disease

Table 2 List of alternative splicing events confirmed using rtPCR

Gene	GenBank accession number (reference transcript*)	GenBank accession number (variant transcript*)	Alternative splicing event: change of mRNA transcript composition in disease state^†	Alternatively spliced region	rtPCR p value
mTLE
CACNB1	NM_000723	NM_199247	NE: 65% ↑ variant/reference ratio	INTRON 6	0.035
CACNB4	NM_000726	AY054985	NE: 4.2x ↑ variant/reference ratio	INTRON 2	0.027
CLCN7	NM_001287	AK096963	IR: 65% ↓ variant/total ratio	INTRON 18	<0.001
FXYD6	NM_022003	BP372334	NE: 22% ↓ variant/reference ratio	INTRON 1	<0.001
GRIA1	NM_000827	A46050	NE: 62% ↓ variant/reference ratio	INTRON 14	0.002
KCNK1	NM_002245	AV733795	PIED: 13% ↓ variant/total ratio	EXON 2	<0.001
KCNQ2	NM_004518	AY358189	NE: 34% ↓ variant/total ratio	INTRON 7	<0.001
MCOLN1	NM_020533	CA489568	ASD: 47% ↑ variant/reference ratio	EXON 7	<0.001
AD
CACNA1G	NM_018896	NM_198376	PIED: 67% ↓ variant/total ratio	EXON 36	<0.001
GABRA6	NM_000811	AK090735	IR: 30% ↓ variant/reference ratio	INTRON 6	0.007
GRIA1	NM_000827	A46050	NE: 2.5x ↑ variant/reference ratio	INTRON 14	0.001
KCNAB1	NM_172160	NM_172159	NE: 75% ↓ variant/reference ratio	INTRON 1	0.004
KCNN1	NM_002248	BM718136	ASD: 25% ↓ variant/reference ratio	EXON 6	<0.001
KCNN2	NM_021614	BG769522	ES: 85% ↓ variant/reference ratio	EXON 3	0.002
MCOLN1	NM_020533	CA489568	ASD: 19% ↑ variant/reference ratio	EXON 7	0.016

*Reference transcript refers to traditionally spliced gene product, while the variant refers to the alternatively spliced mRNA transcript. ^†Splice array determined results were confirmed using quantitative rtPCR in a larger sample size (control (n = 28-29) versus mTLE neocortex (n = 43); control (n = 27) versus AD (n = 31) temporal cortex and cerebellum). ASA, alternative splice acceptor site; ASD, alternative splice donor site; ES, exon skipped; EsS, exons skipped; IR, intron retention; NE, novel exon; NEs, novel exons; PIED, partial internal exon deletion.

ISSN: 1474-760X